title: Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells.
abstract: BACKGROUND
  The concept of combination of chemoprevention holds great potential for cancer management as lower, clinically tolerable doses of individual agents could be achieved through therapeutic synergy. However, elucidation of their possible interactions--additive, synergistic, or antagonistic--must be thoroughly studied before considering for clinical use.
  
  
  METHODS
  To evaluate the effect of combination treatment of sulforaphane (SFN) and eugenol on HeLa cells, the authors performed cell viability assay, apoptosis assay, and reverse transcription polymerase chain reaction for gene expression analysis. Calculations of combination effects were expressed as a combination index (CI) with CI < 1, CI = 1, or CI > 1 representing synergism, additivity, or antagonism, respectively.
  
  
  RESULTS
  Simultaneous treatment with variable dose combinations of SFN and eugenol resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction. Importantly, gemcitabine used in conjunction with the low- and high-dose combinations showed no significant cell death at lower doses suggesting that cell cytotoxicity is proportional to gemcitabine alone, whereas at higher sublethal doses of SFN and eugenol, it was found to act in a synergistic manner with gemcitabine. Furthermore, SFN and eugenol combinations at synergistic dose significantly downregulated the expression of Bcl-2, COX-2 and IL-β but not the antagonistic combinations.
  
  
  CONCLUSIONS
  This study clearly indicates that 2 (or more) chemopreventive agents can act antagonistically or synergistically necessitating elucidation of possible mechanistic interactions for favorable and reliable outcomes of dietary components in the field of cancer prevention.
authors.affiliation: Department of Biotechnology, Manipal University, Dubai, United Arab Emirates.
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Anita
authors.initials: A
authors.lastname: Priyani
authors.forename: Lida
authors.initials: L
authors.lastname: Sadrieh
authors.forename: Kruti
authors.initials: K
authors.lastname: Brahmbhatt
authors.forename: Musthaq
authors.initials: M
authors.lastname: Ahmed
authors.forename: Chhavi
authors.initials: C
authors.lastname: Sharma
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005054:Eugenol / Q000008:administration & dosage; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D000093542:Gemcitabine
chemical_list: D016588:Anticarcinogenic Agents; D053583:Interleukin-1beta; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; D013861:Thiocyanates; D003841:Deoxycytidine; D005054:Eugenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C016766:sulforaphane; D000093542:Gemcitabine